Journal of Molecular Modeling

, Volume 18, Issue 7, pp 2917–2927

Large-scale virtual screening for the identification of new Helicobacter pylori urease inhibitor scaffolds

  • Homa Azizian
  • Farzaneh Nabati
  • Amirhossein Sharifi
  • Farideh Siavoshi
  • Mohammad Mahdavi
  • Massoud Amanlou
Original Paper

Abstract

Here, we report a structure-based virtual screening of the ZINC database (containing about five million compounds) by computational docking and the analysis of docking energy calculations followed by in vitro screening against H. pylori urease enzyme. One of the compounds selected showed urease inhibition in the low micromolar range. Barbituric acid and compounds 1a, 1d, 1e, 1f, 1g, 1h were found to be more potent urease inhibitors than the standard inhibitor hydroxyurea, yielding IC50 values of 41.6, 83.3, 66.6, 50, 58.8, and 60 μM, respectively (IC50 of hydroxyurea = 100 μM). 5-Benzylidene barbituric acid has enhanced biological activities compared to barbituric acid. Furthermore, the results indicated that among the substituted 5-benzylidene barbiturates, those with para substitution have higher urease inhibitor activities. This may be because the barbituric acid moiety is closer to the bimetallic nickel center in unsubstituted or para-substituted than in ortho- or meta-substituted analogs, so it has greater chelating ability.

Keywords

Helicobacter pylori Urease inhibitors Virtual screening 5-Benzylidene barbituric acid Docking 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Homa Azizian
    • 1
  • Farzaneh Nabati
    • 1
  • Amirhossein Sharifi
    • 1
  • Farideh Siavoshi
    • 2
  • Mohammad Mahdavi
    • 1
  • Massoud Amanlou
    • 1
    • 3
  1. 1.Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran
  2. 2.Department of Microbiology, Faculty of SciencesUniversity of TehranTehranIran
  3. 3.Drug Design and Development Research CenterTehran University of Medical SciencesTehranIran

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